Amphetamine Regulation of the Norepinephrine Transporter

安非他明对去甲肾上腺素转运蛋白的调节

基本信息

批准号：
7316110
负责人：
KEVIN ERREGER
金额：
$ 4.83万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7316110
关键词：
Amphetamines Anxiety Disorders Attention Behavior Binding Biogenic Amine Neurotransmitters Calcium Cell membrane Cells Chemicals Cocaine Complex Data Dependence Dopamine Extracellular Space Fellowship Functional disorder Individual Investigation Ion Channel Ions Locomotion Major Depressive Disorder Measurement Measures Mediating Membrane Membrane Transport Proteins Mental disorders Modeling Moods Mutation N-terminal Names Nervous System Physiology Nervous system structure Neurons Neurotransmitters Norepinephrine Numbers Phosphorylation Phosphorylation Site Phosphotransferases Physiological Physiology Play Probability Property Proteins Radiolabeled Range Regulation Reporting Resolution Rewards Role SNAP receptor Serotonin Signal Transduction Surface Therapeutic Therapeutic Agents Time Work base drug development drug of abuse ecstasy extracellular kinase inhibitor monoamine neuronal excitability neurotransmitter reuptake noradrenaline transporter norepinephrine system psychostimulant radiotracer reboxetine single molecule syntaxin 1A therapeutic target voltage

项目摘要

Plasma membrane transporters control the active reuptake of neurotransmitters that mediate chemical signaling in the nervous system. Biogenic amine neurotransmitters (i.e. norepinephrine, NE) play a role in a number of physiological functions including autonomic regulation, locomotion, and complex behaviors such as attention and reward. By terminating these chemical signals, monoamine transporters are critical to the efficient function of the nervous system. The NE system has been implicated in a range of mood and anxiety disorders and the development of drugs such as reboxetine specifically targeting the norepinephrine transporter (NET)are promising therapeutic agents. NET is also a target for drugs of abuse such as the psychostimulants cocaine and amphetamine (AMPH). At present there are few reports of high resolution measures of intrinsic transporter function. We propose to use NET currents as one measure of transporter activity, including real-time recordings of unitary transporter currents in excised patches. Transporter currents and substrate flux will be used as functional readouts for transporter regulation by AMPH and a range of other modulators. This work will characterize AMPH regulation of monoamine transporter intrinsic function and regulation, and will also be important in building a framework in which to interpret changes caused by physiological modulators, drugs of abuse, and therapeutic agents.

质膜转运蛋白控制介导化学的神经递质的主动再摄取神经系统中的信号传导。生物胺神经递质（即去甲肾上腺素，NE）在A中起作用生理功能的数量，包括自主法规，运动和复杂行为作为关注和奖励。通过终止这些化学信号，单胺转运蛋白对神经系统的有效功能。 NE系统已与一系列的情绪和焦虑有关疾病和诸如重羧丁等药物的发育专门针对去甲肾上腺素转运蛋白（NET）是有前途的治疗剂。净也是滥用药物的目标心理刺激剂可卡因和苯丙胺（AMPH）。目前，很少有高分辨率的报道内在转运蛋白功能的度量。我们建议将净电流用作转运蛋白的一种度量活动，包括切除斑块中单位转运蛋白电流的实时记录。转运蛋白电流和底物通量将用作AMPH和A的运输蛋白调节的功能读数其他调节器范围。这项工作将表征单胺转运蛋白固有的AMPH调节功能和法规，并且在建立一个解释变化的框架中也很重要由生理调节剂，滥用药物和治疗剂引起的。